PFCs are synthetic chemicals used as surfactants and in surface protection, including stain-resistant products (e.g., carpets and fabrics), nonstick coatings, and food packaging. PFCs are ubiquitous and persistent in the environment and in human tissue. Though present in the environment for decades, PFCs are relatively new compounds of interest with respect to health outcomes and there is mounting evidence from animal and human studies suggesting that they may be developmental toxicants. The primary aim of the proposed research is to investigate the association of prenatal PFC exposure with growth and development in children. We will measure levels of four perfluorinated compounds - perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) - in prenatal maternal plasma collected in early gestation and estimate associations with fetal and infant somatic growth, childhood adiposity and metabolic outcomes such as serum cholesterol and insulin resistance, and neurodevelopment, including cognition and behavior. We will examine associations of PFCs with prenatal maternal and neonatal thyroid hormone levels and explore thyroid function as an underlying pathway for PFC-related associations with growth and neurodevelopment. We will also measure postnatal PFCs in offspring at age 7 to explore their contribution to these outcomes independent of prenatal exposure. We will investigate these aims in Project Viva, a large, well-characterized longitudinal pre-birth cohort of mothers recruited 1999-2002 during pregnancy (approximately 1,700 have archived early pregnancy plasma samples available for PFC analysis) and their offspring (approximately 610 have archived postnatal blood samples available for PFC analysis) followed from birth through age 7 years. We will estimate associations using multivariable regression, controlling for a wide range of covariates. This will be the largest study to date to assess the effect of prenatal PFCs on childhood growth and development the first study to account for prenatal and postnatal PFCs. This highly cost-effective investigation will benefit from the use of a well-characterized population assessed longitudinally since early pregnancy for whom a wealth of information on risk factors for adverse child development has already been collected. Recruitment of pregnant mothers during 1999-2002 coincides with the period of peak PFC emissions, enhancing our power to detect exposure effects. Results will further our understanding of the impact of prenatal and postnatal exposure to PFCs on growth and development during the prenatal and early childhood period. This is a major public health concern given the ubiquity and persistence of these chemicals in the environment and in humans and their potential role as developmental toxicants. PUBLIC HEALTH RELEVANCE: Polyfluoroalkyl chemicals (PFCs) are widely used in industrial and consumer products, such as food packaging, and stain-resistance coatings for carpet and furniture, yet little is known about their effect on human health. This study will be an important contribution to the literature necessary for informing the public about the potential hazard associated with prenatal and postnatal PFCs on fetal and childhood growth and neurodevelopment.